8VII

EgtB-IV from Crocosphaera subtropica, an ergothioneine-biosynthetic type IV sulfoxide synthase in complex with cysteine and hercynine

Summary for 8VII

• Entry DOI: 10.2210/pdb8vii/pdb
• Related: 8VIG 8VIH 8VIK 8VIL
• Descriptor: Sulfoxide synthase EgtB-IV, SODIUM ION, MANGANESE (II) ION, ... (7 entities in total)
• Functional Keywords: ergothioneine, sulfoxide, sulfur, non-heme iron, oxidoreductase
• Biological source: Crocosphaera subtropica ATCC 51142
• Total number of polymer chains: 2
• Total formula weight: 110769.72

Authors

Ireland, K.A.,Davis, K.M. (deposition date: 2024-01-04, release date: 2024-08-07, Last modification date: 2024-09-11)

Primary citation

Ireland, K.A.,Kayrouz, C.M.,Abbott, M.L.,Seyedsayamdost, M.R.,Davis, K.M.
Structural insights into the convergent evolution of sulfoxide synthase EgtB-IV, an ergothioneine-biosynthetic homolog of ovothiol synthase OvoA.
Structure, 2024

PubMed Abstract: Non-heme iron-dependent sulfoxide/selenoxide synthases (NHISS) constitute a unique metalloenzyme class capable of installing a C-S/Se bond onto histidine to generate thio/selenoimidazole antioxidants, such as ergothioneine and ovothiol. These natural products are increasingly recognized for their health benefits. Among associated ergothioneine-biosynthetic enzymes, type IV EgtBs stand out, as they exhibit low sequence similarity with other EgtB subfamilies due to their recent divergence from the ovothiol-biosynthetic enzyme OvoA. Herein, we present crystal structures of two representative EgtB-IV enzymes, offering insights into the basis for this evolutionary convergence and enhancing our understanding of NHISS active site organization more broadly. The ability to interpret how key residues modulate substrate specificity and regioselectivity has implications for downstream identification of divergent reactivity within the NHISS family. To this end, we identify a previously unclassified clade of OvoA-like enzymes with a seemingly hybrid set of characteristics, suggesting they may represent an evolutionary intermediate between OvoA and EgtB-IV.

PubMed: 39216472
DOI: 10.1016/j.str.2024.08.006

Experimental method

X-RAY DIFFRACTION (1.621 Å)